2-decarboxy-2-alkylcarbonyl-9-deoxy-9,10-didehydro-pgd compounds

ABSTRACT

The present invention provides novel prostaglandin analogs wherein the C-2 carboxyl is replaced by alkylcarbonyl, i.e., a C-2 ketone. These novel 2-decarboxy-2-alkylcarbonyl-PG-type compounds are disclosed as improved gastrointestinal cytoprotective agents, being devoid or substantially devoid of other prostaglandin-type effects (e.g., smooth muscle or cardiovascular).

The present application is a divisional application of Ser. No. 888,695,filed Mar. 21, 1978, now U.S. Pat. No. 4,123,463.

The present invention relates to prostaglandin analogs, for which theessential material constituting disclosure therefor is incorporated byreference here from U.S. Pat. No. 4,123,463.

I claim:
 1. A prostaglandin analog of the formula ##STR1## wherein D is##STR2## wherein R₁ is alkyl of one to 4 carbon atoms, inclusive;WHEREIN L₁ is ##STR3## A MIXTURE OF ##STR4## wherein R₃ and R₄ arehydrogen, methyl, or fluoro, being the same or different, with theproviso that one of R₃ and R₄ is methyl only when the other is hydrogenor methyl;Wherein M₁ is ##STR5## wherein R₅ is hydrogen or methyl;WHEREIN R₇ is ##STR6## WHEREIN H IS ZERO TO THREE, INCLUSIVE, WHEREIN MIS ONE TO 5, INCLUSIVE, S IS ZERO, ONE, 2, OR 3, AND T is chloro,fluoro, trifluoromethyl, alkyl of one to 3 carbon atoms or alkoxy of oneto 3 carbon atoms, the variout T's being the same or different, with theproviso that not more than two T's are other than alkyl; Wherein Y₁is(1) trans--CH═CH--, (2) cis--CH═CH--, (3) --ch₂ ch₂ --, or (4)--C.tbd.C--; and Wherein Z₁ is(1) cis--CH═CH--CH₂ --(CH₂)_(g) --CH₂ --,(2) cis--CH═CH--CH₂ --(CH₂)_(g) --CF₂ --, (3) cis--CH₂--CH═CH--(CH₂)_(g) --CH₂ --, (4) --(ch₂)₃ --(ch₂)_(g) --CH₂ --, (5)--(ch₂)₃ --(ch₂)_(g) --CF₂ --, (6) --ch₂ --o--ch₂ --(ch₂)_(g) --CH₂ --,(7) --(ch₂)₂ --o--(ch₂)_(g) --CH₂ --, (8) --(ch₂)₃ --o--(ch₂)_(g) --,(9) --C.tbd.C--CH₂ --(CH₂)_(g) --CH₂ --, (10) --ch₂ --c.tbd.c--(ch₂)_(g)--CH₂ --, or (11) trans--(CH₂)₂ --(CH₂)_(g) --CH.tbd.CH--, wherein g isone, two, or three.
 2. A prostaglandin analog according to claim 1,wherein R₁ is methyl.
 3. A prostaglandin analog according to claim 2,wherein D is ##STR7## 4.2-Decarboxy-2-methylcarbonyl-9-deoxy-9,10-didehydro-8β, 12α-PGD₂, aprostaglandin analog according to claim
 3. 5. A prostaglandin analogaccording to claim 2, wherein D is ##STR8##
 6. A prostaglandin analogaccording to claim 5, wherein Y₁ is cis--CH═CH--. 7.2-Decarboxy-2-methylcarbonyl-13-cis-9-deoxy-9,10-didehydro-PGD₂, aprostaglandin analog according to claim
 6. 8. A prostaglandin analogaccording to claim 5, wherein Y₁ is --CH₂ CH₂ --. 9.2-Decarboxy-2-methylcarbonyl-13,14-dihydro-9-dihydro-9-deoxy-9,10-didehydro-PGD₂,a prostaglandin analog according to claim
 8. 10. A prostaglandin analogaccording to claim 5, wherein Y₁ is --C.tbd.C--. 11.2-Decarboxy-2-methylcarbonyl-13,14-didehydro-9-deoxy-9,10-didehydro-PGD₂,a prostaglandin analog according to claim
 10. 12. A prostaglandin analogaccording to claim 5, wherein Y₁ is trans--CH═CH--.
 13. A prostaglandinanalog according to claim 12, wherein R₇ is ##STR9## 14.2-Decarboxy-2-methylcarbonyl-17-phenyl-18,19,20-trinor-9-deoxy-9,10-didehydro-PGD₂,a prostaglandin analog according to claim
 13. 15. A prostaglandin analogaccording to claim 12, wherein R₇ is ##STR10## 16.2-Decarboxy-2-methylcarbonyl-16-phenoxy-17,18,19,20-tetranor-9-deoxy-9,10-didehydro-PGD₂,a prostaglandin analog according to claim
 15. 17. A prostaglandin analogaccording to claim 12, wherein R₇ is --(CH₂)_(m) --CH₃ --.
 18. Aprostaglandin analog according to claim 17, wherein Z₁ iscis--CH═CH--CH₂ --(CH₂)_(g) --CF₂ --. 19.2-Decarboxy-2-methylcarbonyl-2,2-difluoro-9-deoxy-9,10-didehydro-PGD₂, aprostaglandin analog according to claim
 18. 20. A prostaglandin analogaccording to claim 17, wherein Z₁ is cis--CH₂ --CH--CH--(CH₂)_(g) --CH₂--. 21.2-Decarboxy-2-methylcarbonyl-cis-4,5-didehydro-16,16-dimethyl-9-deoxy-9,10-didehydro-PGD₁,a prostaglandin analog according to claim
 20. 22. A prostaglandin analogaccording to claim 17, wherein Z₁ is --(CH₂)₃ --(CH₂)_(g) --CH₂ --. 23.2-Decarboxy-2-methylcarbonyl-9-deoxy-9,10-didehydro-PGD₁, aprostaglandin analog according to claim
 22. 24. A prostaglandin analogaccording to claim 17, wherein Z₁ is --(CH₂)₃ --(CH₂)_(g) --CF₂ --. 25.2-Decarboxy-2-methylcarbonyl-2,2-difluoro-9-deoxy-9,10-didehydro-PGD₁, aprostaglandin analog according to claim
 24. 26. A prostaglandin analogaccording to claim 17, wherein Z₁ is --CH₂ --O--CH₂ --(CH₂)_(g) --CH₂--.
 27. 2-Decarboxy-2-methylcarbonyl-5-oxa-9-deoxy-9,10-didehydro-PGD₁,a prostaglandin analog according to claim
 26. 28. A prostaglandin analogaccording to claim 17, wherein Z₁ is --(CH₂)₂ --O--(CH₂)_(g) --CH₂ --.29. 2-Decarboxy-2-methylcarbonyl-4-oxa-9-deoxy-9,10-didehydro-PGD₁, aprostaglandin analog according to claim
 28. 30. A prostaglandin analogaccording to claim 17, wherein Z₁ is --(CH₂)₃ --O--(CH₂)_(g) --. 31.2-Decarboxy-2-methylcarbonyl-3-oxa-9-deoxy-9,10-didehydro-PGD₁, aprostaglandin analog according to claim
 30. 32. A prostaglandin analogaccording to claim 17, wherein Z₁ is --C.tbd.C--CH₂ --(CH₂)_(g) --CH₂--. 33.2-Decarboxy-2-methylcarbonyl-5,6-didehydro-9-deoxy-9,10-didehydro-PGD₂,a prostaglandin analog according to claim
 32. 34. A prostaglandin analogaccording to claim 17, wherein Z₁ is cis--CH₂ --C.tbd.C--(CH₂)_(g) --CH₂--. 35.2-Decarboxy-2-methylcarbonyl-4,4,5,5-tetradehydro-9-deoxy-9,10-didehydro-PGD₁,a prostaglandin analog according to claim
 34. 36. A prostaglandin analogaccording to claim 17, wherein Z₁ is trans-(CH₂)₂ --(CH₂)_(g) --CH═CH--.37.2-Decarboxy-2-methylcarbonyl-trans-2,3-didehydro-9-deoxy-9,10-didehydro-PGD₁,a prostaglandin analog according to claim
 36. 38. A prostaglandin analogaccording to claim 17, wherein Z₁ is cis--CH═CH--CH₂ --(CH₂)_(g) --CH₂--.
 39. A prostaglandin analog according to claim 38, wherein R₅ ismethyl. 40.2-Decarboxy-2-methylcarbonyl-15-methyl-9-deoxy-9,10-didehydro-PGD₂, aprostaglandin analog according to claim
 38. 41. A prostaglandin analogaccording to claim 38, wherein R₅ is hydrogen.
 42. A prostaglandinanalog according to claim 41, wherein one of R₃ and R₄ is fluoro. 43.2-Decarboxy-2-methylcarbonyl-16,16-difluoro-9-deoxy-9,10-didehydro-PGD₂,a prostaglandin analog according to claim
 42. 44. A prostaglandin analogaccording to claim 41, wherein at least one of R₃ and R₄ is methyl. 45.2-Decarboxy-2-methylcarbonyl-16,16-dimethyl-9-deoxy-9,10-didehydro-PGD₂,a prostaglandin analog according to claim
 44. 46. A prostaglandin analogaccording to claim 41, wherein R₃ and R₄ are both hydrogen. 47.2-Decarboxy-2-methylcarbonyl-9-deoxy-9,10-didehydro-PGD₂, aprostaglandin analog according to claim 46.